Humans and animals are in continuous contact with microorganisms. Generally, because of the effectiveness of host defense mechanisms these microorganisms do not cause disease. However, some microorganisms (e.g., opportunistic pathogens) can become infective in particular types of individuals, such as those who are immunocompromised. Still other microorganisms are extremely virulent upon contact. For example, microorganisms such as the Ebola virus are associated with close to 100% fatality rates.
Traditional methods of correlating disease symptoms with the presence of a microorganism rely on identifying through symptoms and/or through epidemiological studies, the likelihood that the disease is caused by an infectious agent and attempting to culture appropriate samples from the individual to isolate and identify the agent. This can be problematic where epidemiological evidence is unclear, particularly in the case of pathogens with long incubation periods (e.g., up to 10 years in the case of HIV and 20–30 years in the case of Mycobacterium leprae).
Even where epidemiological evidence suggests an infectious cause for a disease, the microorganisms responsible for these diseases can evade detection. For example, Whipple's disease, a debilitating disease associated with diarrhea and weight loss, was for many years described as “intestinal lipodystrophy” because no microorganism could be cultured from samples from patients with disease. However, the microbial origin of Whipple's was suggested by the dramatic response of patients to antibiotics and the presence of bacilli observed in electron micrographs of affected tissues. Still, the identification of the infectious organism as an actinomycetes awaited the advent of molecular techniques such as PCR. See, e.g., Maiwald et al., Clin. Infect. Dis. 32(3): 457–463 (2001). PCR amplification of conserved ribosomal sequences also led to the detection of another unculturable bacteria, the causative agent of bacillary angiomatosis which is associated with the proliferation of small blood vessels in the skin and visceral organs of patients with AIDS (see, Relman et al., New Engl. J. Med. 323: 1573–1580 (1990)). Another molecular technique, the DNA subtractive cloning method—representational difference analysis (Lisitsyn, Trends Genetics 11: 303–307 (1995)), enabled the discovery of the herpesvirus causing Kaposi's sarcoma (Chang et al., Science 265: 1865–1869 (1994)).
A high throughput approach to identifying infectious organisms has been described by Cummings and Relman, Emerg. Infect. Dis. 6(5): 513–25 (2000). Cummings and Relman report using a DNA microarray comprising sequences from known pathogens to detect the presence pathogens in patient samples. However, the method will only be able to detect pathogens for which at least some sequence information is known.